Exchange Nephropathies (oxaluria)

Exchange, or dismetabolic, nephropathies in a broad sense - diseases associated with severe violations of water-salt metabolism and other types of metabolism of the whole organism. Dysmetabolic nephropathy in the narrow sense is a polygenically inherited pathology of oxalic acid metabolism and is manifested in conditions of familial instability of cell membranes. Exchange nephropathies are divided into primary ones - the result of kidney damage by products of altered metabolism throughout the body, and secondary, associated with the disruption of enzyme systems in the kidneys themselves.

Primary oxaluria.

The source of most of the oxalates is endogenous processes. The precursors of oxalates are glycine, phenylalanine, tyrosine, tryptophan, threonine, asparagine and ascorbic acid. A large endogenous source of oxalates is ethanolamine. Additional conditions for endogenous hyperproduction of oxalates - deficiency of vitamins A, D, B ₆, taurine. All the precursors are converted to oxalic acid through glyoxyl. Of particular importance is the increased absorption of oxalates in the intestine. Clinical forms of primary endogenous metabolic disturbances of oxalic acid are oxalose and hyperoxaluria with nephrolithiasis. Biochemically distinguish two types, both inherited are autonomic-recessive.

1. Deficiency of glyoxyl acid carbo- lidase, which catalyzes the conversion of glyoxylate to CO ₂ and formic acid. The cofactor of this reaction is thiamine. In this variant of the defect with urine, large amounts of oxalic, glycolic and glyoxylic acids are released.
2. Defect in the enzymatic system of D-glycerate dehydrogenase. In such cases, a large amount of oxalic and glyceric acids is excreted in the urine. Both enzyme systems function in the liver. Clinically, the two options are not distinguishable.

In both cases, relatives of probands often have various kidney lesions. In maternal midwifery, miscarriages and stillbirths are noted. Oxalosis is more common in boys. The first manifestations of the disease in 65% of patients appear before the age of 5, 80% do not live to 20 years. The earlier the disease manifested itself, the worse the prognosis - the shorter the life of the patient. The first manifestations of this pathology are changes in urine analysis in the form of proteinuria and hematuria, renal colic, recurrent course of pyelonephritis, is possible. Lithiasis is mainly bilateral, recurring with coral stones. A delay in physical development, osteoporosis, changes in the myocardium, cardiac conduction, arthralgia are described. Chronic renal failure rapidly develops to the terminal stage. Oxalosis is a rare clinical form of primary oxaluria. A little more than 100 documented cases of generalized oxalose have been described in the literature. Significantly more common primary isolated hyperoxaluria. Its course is somewhat milder and chronic renal failure develops later than with oxalose. However, the forecast is also poor. Since the defect is localized in the enzyme systems of the liver, transplantation of an isolated kidney is useless. At present, attempts are being made to transplant the liver-kidney block.

Secondary hyperoxaluria. Oxalate-calcium crystalluria

Oxalate-calcium crystalluria is a frequent phenomenon. There are several groups of its causes. One of them - increased precipitation of calcium oxalate in urine. Urine is always a saturated solution of calcium oxalate, since at ordinary pH values of urine close to 7 (5.5-7.2), the solubility of calcium oxalate is negligible - 0.56 mg per 100 ml of water. The maximum solubility of calcium oxalate reaches below pH 3.0. The degree of precipitation depends on the ratio of calcium and oxalates (individuals with hypercalciuria excrete more calcium oxalate); from the presence of magnesium salts (magnesium deficiency precipitation increases); from the excess or lack of substances that support the colloidal properties of urine (citrates, celatin, pyrophosphates); from excessive excretion of oxalates.

Excessive excretion of oxalates can be associated with excess production of oxalates (most often not associated with genetically caused liver enzyme defects), with increased absorption of oxalates in the intestine, and with local formation of oxalates in the renal tubules themselves. Excess production of oxalates is possible in conditions of deficiency of vitamins A and D, as well as in exogenous deficiency or endogenous metabolic disturbance of pyridoxine. At the same time, a deficiency of taurine and taurocholic acids develops, and as a consequence, the metabolism of glycocholic acid changes toward excessive production of oxalate. In patients with impaired uric acid metabolism (hyperuricemia) oxalate stones are frequent. 80% of patients with gout have an increased concentration of oxalic acid in the blood.

Increased absorption of oxalates in the intestine is possible because of the large consumption of foods rich in oxalic acid salts. These include deciduous vegetables (lettuce, sorrel, spinach), tomato and orange juice, beets. Genetically determined enterooxalate syndrome, or Loka syndrome, is described, in which the increased absorption of oxalates in the intestine depends little on their consumption. Local formation of oxalates in the kidneys is the most common cause of mild oxaluria and increased crystal formation in the urine. It is known that cell membranes, including tubular epithelial cells, consist of interpenetrating layers of proteins and phospholipids. The outer layer of the cell membrane facing the lumen of the tubule is formed mainly by phosphatidylserine and phosphatidylethanolamine. When phospholipase is activated, the nitrogenous bases (series and ethanolamine) are cleaved from the membrane and converted into oxalate by a short metabolic chain. The latter combines with calcium ions and is converted to calcium oxalate. The activation of endogenous or the appearance of bacterial phospholipases is an integral component of the inflammation reaction. Increased excretion of calcium oxalate and crystalluria are always present in the urine of patients in the active phase of pyelonephritis, which makes it impossible to diagnose dysmetabolic nephropathy according to the type of oxaluria before the inflammation subsides. Increased activity of phospholipases always accompanies ischemia of kidneys of any nature and processes of activation of peroxidation of proteins and lipids. The instability of cell membranes with increased activity of phospholipases is a condition described as a polygenically inherited trait. Hyperoxaluria and crystalluria often accompany any manifestations of allergosis, especially - respiratory allergosis. The presence of oxalate diathesis is discussed.

Markers of calciphylaxis: phospholipiduria, increased excretion of ethanolamine in the urine, high activity of phospholipase C in the urine, increased excretion of crystal-forming anions - oxalates and phosphates.

Treatment of secondary hyperoxaluria

An abundant drink is prescribed (up to 2 liters per 1.73 m ² ), especially in the evening, before bedtime. We recommend a potato-cabbage diet rich in potassium, poor in salts of oxalic acid. Products containing a large number of oxalates (leafy vegetables, beets, tomato and orange juice) are limited. Useful foods enriched with potassium and magnesium are dried fruits, bread with bran, pumpkin, zucchini, eggplant, dogwood, as well as fresh unsweetened fruits. Medication therapy involves the appointment in the spring and autumn - in seasons of natural enhancement of oxaluria - monthly courses of membrane stabilizers. Assign vitamins A, B ₆, complex preparations containing vitamin E in combination with other components of the antioxidant system, as well as small doses of magnesium (panangin or asparks). With a pronounced and persistent hyperoxaluria, dimephosphate courses are indicated - xidiphon or dimephosphon.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12]